**5.1. Conventional therapy**

has had at least one hypomanic, but no manic or mixed episodes, and one major depressive episode. Bipolar II disorder may also include psychotic symptoms during the severe depressive episodes. Bipolar I disorder leads to hospitalizations, need for treatment, and decline in daily functioning more often compared with bipolar II disorder [28, 29]. Similarly, the major depressive disorder with psychotic features is diagnosed when the criteria for major depressive disorder episode are met and delusions or hallucinations occur within the episode. Mood-congruent delusions or hallucinations are consistent with the depressive themes (delusions of guilt, delusions of deserved punishment, nihilistic delusions etc.). Mood-incongruent delusions or hallucinations do not have any apparent relationship to depressive themes (persecutory delusions, delusions of thought insertion, delusions of control etc.) [30]. For the substance-induced psychotic disorders, the victim is characterized by prominent hallucinations or delusions that are judged to be due to the direct physiological effects of a substance (drug of abuse, a medication, or a toxin exposure). Substance-induced psychotic disorders are distinguished from the substance-induced delirium (clear consciousness), from substance intoxication or withdrawal with perceptual disturbances (more persistent, clinically relevant symptoms, and the individual is void of insight) and from primary psychotic disorders [31]. The onset of substance use typically precedes the onset of psychotic symptoms, and the symptoms should disappear within 1 month after the substance use has ceased. Psychotic symptoms may occur during withdrawal or intoxication of these substances: cannabis, inhalants, hypnotics, hallucinogens, amphetamine, opioids, cocaine, alcohol, anxiolytics, phencyclidine and sedatives [32]. Some medications (e.g. antiparkinsonian medications, corticosteroids, anticholinergic agents, antimalarial medications and chemotherapeutic agents) can also trigger symptoms of psychosis. The clinical picture of psychosis varies depending on the substance [12]. For the one resulting from a general medical condition, the victim feels hallucinated or delusioned. These symptoms can be judged to result from the direct physiological impacts of a general medical condition, and they are not explained by any other mental disorder [33]. Clear temporal association should be found between the general medical issue and the onset of psychotic disturbance. Additionally, there must be literature evidence on the particular medical condition causing psychotic symptoms [34]. Examples of general medical conditions that can cause psychotic symptoms include temporal lobe epilepsy, brain lesions and tumors, central nervous system infections and any severe medical condition requiring treatment in intensive care unit [34, 35]. Delirium is a condition characterized by disturbance of consciousness and cognition which may have psychotic symptoms as an associated feature [36, 37]. The etiology of delirium varies, including substance-induced delirium and delirium due to underlying general medical issues. Irrespective of the cause, associated challenges emanate within the shortest time possible and usually not consistent during the course of the

72 Psychosis - Biopsychosocial and Relational Perspectives

day [37–39].

**3. Conventional treatment and management options**

Many of the drugs that have been introduced for the treatment of psychotic disorders are known to interfere with the normal physiological actions of several of the brain neurotransmitters and their receptors. The major brain neurotransmitters that have been implicated in Contrary to phytotherapy that involves the use of medicinal plants, conventional therapy for psychosis is majorly by the use of medications. Others include cognitive therapy treatment, counseling, family or support group, the use of mood stabilizers etc. Cognitive therapy centers on identifying different patterns of thought (perception about situation) that brings about undesirable action or feelings. In some countries of the world particularly United Kingdom and United States, this kind of therapy is embraced (sometimes in combination with medications) as the most effective way of treating psychosis or psychosis-related disorder such as schizophrenia, depression and or substance abuse. Additionally, family or support group form of psychosis therapy deals with the informal measure of treatment by a way of caring or providing support to people or family members suffering from the menace geared towards knowing how they fare on the various treatment or medications being exposed to and perhaps discussion on whether there is need for a change if medication is presenting havoc than alleviating the situation.

higher affinities for other neuroreceptors such as serotonin (e.g. 5-HT1A, 5-HT2A etc.) and norepinephrine (α1, α2 subtypes) as well as regulate glutamate receptor-mediated functions and behaviors among others [51, 52]. However, it is interesting to note that with issues relating to pharmacological effect, efficacy, safety, tolerability, cost effectiveness and adverse effects, it is important to weigh the pros and cons between both sides in terms of the above enumerated factors. In fact, there are reports that these newer generation drugs are more expensive, although the benefits they rendered outweighs the financial implications and are of less consequence as highlighted by clinicians and policy makers [51]. Similarly, despite revelations of side effects such as weight gain attributed to some modern class of antipsychotics such as Clozapine and Olanzapine but evidence as to why this is so is still unclear. Above all, in a review by Gardner and others [45] at comparing the superiority between typical and atypical antipsychotics taking into consideration above factors, they affirm the supremacy of the atypical antipsychotics over the old ones as evidenced in a number of cited reports (though accompanied with limitations) but still,

The Ambit of Phytotherapy in Psychotic Care http://dx.doi.org/10.5772/intechopen.79547 75

Herbal medicine or phytotherapy according to World Health Organization (WHO) means herbal (medicinal plant) product containing the active components of plant parts or materials or both combined. In recent times, the use of medicinal plants in complementary and alternative medicine has continued to receive wider publicity in many quarters of the world. In fact 80% of the entire global population makes use of one form of traditional medicine in the prevention, diagnosis and treatment of numerous diseases facing them while also being incorporated within their national healthcare system. Psychosis, a mental condition resulting in the ability of an individual to witness distorted or total loss of contact with reality is considered among the neuropsychiatric disorders according to WHO with 13–49% of individual worldwide being affected by them at a particular stage within their life time [13]. Many medicinal plants and orthodox medicines are embraced and used in the management of this derangement [13, 45, 56], despite the numerous adverse effects including but not limited to restlessness, sexual dysfunction, extrapyramidal (EPSs) such as tardive dyskinesia (persistent tongue, mouth and jaw movement), malignant syndrome etc. attributed to these chemical moieties [51]. Interestingly, it is worthy of mention that out of several medicinal plants with reported antipsychotic effect [13, 11], very few, such as Lemon balm (*Melissa officinalis*), Yokukansan (TJ-54), Ginkgo (*Ginkgo biloba*), Valerian (*Valeriana officinalis*), St John's wort (*Hypericum perforatum*), Kava-kava (*Piper methysticum*) have been developed as agents with reported use for phytotherapy while being functioning as antidote against prominent psychiatric ailments (depressive, somatic, psychotic, anxiety, sleep) [5, 57] with the latter four agents among the first 10 best-selling herbal formulations in the US [13] and Africa in the management of neurological diseases [58], although, there are reports of agent like St John's wort inducing psychosis [59, 60]. In fact, despite their wide usage and preference over conventional antipsychotic drugs with varying adverse effects [61], psychiatric patients have continued to adopt herbal therapy for the management of psychosis [11]. The respective list of selected medicinal plants commonly used in psychotic care and the most prominently impli-

cated phytonutrients of antipsychotic significance are presented in **Tables 2** and **3**.

generated huge number of prescriptions and acceptance globally [53–55].

**5.3. Phytotherapy in psychotic care**

### **5.2. Medications as a form of therapy for psychosis**

The discovery of chlorpromazine in the mid-1900s (1953) for the treatment of psychosis or related ailments led to the emergence of other conventional or typical antipsychotics such as perphenazine (marketed in 1957), trifluoperazine (1958), fluphenazine (1960), haloperidol (1966), thiothixene (1968), loxapine (1978), flupentixol (1983) usually referred as the first line or first generation antipsychotics [45]. These traditional agents aside exhibiting different level of potencies such as low (e.g. chlorpromazine), intermediate (perphenazine), high (haloperidol) are embraced and adopted for short or long-term use against acute or chronic psychotic disorders (schizophrenia, schizoaffective and or delusional disorders, psychotic-depressive ailments, dementia etc.). Antipsychotics or neuroleptics (derived from the combination of neuron and 'lepsis' to mean 'take hold of nervous system') ordinarily acts by blocking the Dopamine D<sup>2</sup> receptors (protein) domicile in the limbic system and striatum, thus, producing adverse effects such as the development of extrapyramidal side effects (EPSs), hyperprolactemia (elevated level of prolactin in the blood), neuroleptic malignant with Tardive dyskinesia, sexual dysfunction, restlessness, stiffness and shaking of the joints etc. among common names or features of these effects [50, 51].Moreover, the coming of the newer or modern or second generation antipsychotic drugs (**Table 1**) otherwise referred to as atypical antipsychotics have in a way in recent times in clinical medicine replaced the use of first generation (FG) counterpart owing to their ability to lower some of the side effects known with FG. They exert these actions by proffering less affinity for D<sup>2</sup> receptor,


**Table 1.** Modern antipsychotics.

higher affinities for other neuroreceptors such as serotonin (e.g. 5-HT1A, 5-HT2A etc.) and norepinephrine (α1, α2 subtypes) as well as regulate glutamate receptor-mediated functions and behaviors among others [51, 52]. However, it is interesting to note that with issues relating to pharmacological effect, efficacy, safety, tolerability, cost effectiveness and adverse effects, it is important to weigh the pros and cons between both sides in terms of the above enumerated factors. In fact, there are reports that these newer generation drugs are more expensive, although the benefits they rendered outweighs the financial implications and are of less consequence as highlighted by clinicians and policy makers [51]. Similarly, despite revelations of side effects such as weight gain attributed to some modern class of antipsychotics such as Clozapine and Olanzapine but evidence as to why this is so is still unclear. Above all, in a review by Gardner and others [45] at comparing the superiority between typical and atypical antipsychotics taking into consideration above factors, they affirm the supremacy of the atypical antipsychotics over the old ones as evidenced in a number of cited reports (though accompanied with limitations) but still, generated huge number of prescriptions and acceptance globally [53–55].

### **5.3. Phytotherapy in psychotic care**

depression and or substance abuse. Additionally, family or support group form of psychosis therapy deals with the informal measure of treatment by a way of caring or providing support to people or family members suffering from the menace geared towards knowing how they fare on the various treatment or medications being exposed to and perhaps discussion on whether there is need for a change if medication is presenting havoc than alleviating the situation.

The discovery of chlorpromazine in the mid-1900s (1953) for the treatment of psychosis or related ailments led to the emergence of other conventional or typical antipsychotics such as perphenazine (marketed in 1957), trifluoperazine (1958), fluphenazine (1960), haloperidol (1966), thiothixene (1968), loxapine (1978), flupentixol (1983) usually referred as the first line or first generation antipsychotics [45]. These traditional agents aside exhibiting different level of potencies such as low (e.g. chlorpromazine), intermediate (perphenazine), high (haloperidol) are embraced and adopted for short or long-term use against acute or chronic psychotic disorders (schizophrenia, schizoaffective and or delusional disorders, psychotic-depressive ailments, dementia etc.). Antipsychotics or neuroleptics (derived from the combination of neuron and 'lepsis' to mean

domicile in the limbic system and striatum, thus, producing adverse effects such as the development of extrapyramidal side effects (EPSs), hyperprolactemia (elevated level of prolactin in the blood), neuroleptic malignant with Tardive dyskinesia, sexual dysfunction, restlessness, stiffness and shaking of the joints etc. among common names or features of these effects [50, 51].Moreover, the coming of the newer or modern or second generation antipsychotic drugs (**Table 1**) otherwise referred to as atypical antipsychotics have in a way in recent times in clinical medicine replaced the use of first generation (FG) counterpart owing to their ability to lower some of the

side effects known with FG. They exert these actions by proffering less affinity for D<sup>2</sup>

**Antipsychotics Brand name Year of first market**

Clozapine Clozaril 1991 Olanzapine Zyprexa 1996 Quetiapine Seroquel 1998 Risperidone Risperdal 2004 Ziprasidone Zeldox 2009 Aripiprazole Abilify 2013 Asenapine Saphris 2009 Iloperidone\* Zomaril 2009 Blonanserin Lonasen 2009 Lurasidone\* Latuda 2010

Not yet approved by Food, Drug and Administration (FDA, US).

\*

**Table 1.** Modern antipsychotics.

receptors (protein)

receptor,

'take hold of nervous system') ordinarily acts by blocking the Dopamine D<sup>2</sup>

**5.2. Medications as a form of therapy for psychosis**

74 Psychosis - Biopsychosocial and Relational Perspectives

Herbal medicine or phytotherapy according to World Health Organization (WHO) means herbal (medicinal plant) product containing the active components of plant parts or materials or both combined. In recent times, the use of medicinal plants in complementary and alternative medicine has continued to receive wider publicity in many quarters of the world. In fact 80% of the entire global population makes use of one form of traditional medicine in the prevention, diagnosis and treatment of numerous diseases facing them while also being incorporated within their national healthcare system. Psychosis, a mental condition resulting in the ability of an individual to witness distorted or total loss of contact with reality is considered among the neuropsychiatric disorders according to WHO with 13–49% of individual worldwide being affected by them at a particular stage within their life time [13]. Many medicinal plants and orthodox medicines are embraced and used in the management of this derangement [13, 45, 56], despite the numerous adverse effects including but not limited to restlessness, sexual dysfunction, extrapyramidal (EPSs) such as tardive dyskinesia (persistent tongue, mouth and jaw movement), malignant syndrome etc. attributed to these chemical moieties [51]. Interestingly, it is worthy of mention that out of several medicinal plants with reported antipsychotic effect [13, 11], very few, such as Lemon balm (*Melissa officinalis*), Yokukansan (TJ-54), Ginkgo (*Ginkgo biloba*), Valerian (*Valeriana officinalis*), St John's wort (*Hypericum perforatum*), Kava-kava (*Piper methysticum*) have been developed as agents with reported use for phytotherapy while being functioning as antidote against prominent psychiatric ailments (depressive, somatic, psychotic, anxiety, sleep) [5, 57] with the latter four agents among the first 10 best-selling herbal formulations in the US [13] and Africa in the management of neurological diseases [58], although, there are reports of agent like St John's wort inducing psychosis [59, 60]. In fact, despite their wide usage and preference over conventional antipsychotic drugs with varying adverse effects [61], psychiatric patients have continued to adopt herbal therapy for the management of psychosis [11]. The respective list of selected medicinal plants commonly used in psychotic care and the most prominently implicated phytonutrients of antipsychotic significance are presented in **Tables 2** and **3**.


**Family Species Parts Folkloric** 

Fabaceae *Afzelia Africana* Smith

Fabaceae *Amblygonocarpus* 

Fabaceae *Arachis* 

Fabaceae *Lonchocarpus* 

Lamiaceae *Ocimum* 

Lamiaceae *Mentha* 

*andongensis*

*hypogaea L*

*cyanescens* (Schumach and Thonn.) Benth.

*sanctum L.*

*aquatica* L.

**usage**

Fresh stembark of *Lophira alata* and *A. africana* are powdered together. The powder is then infused in water for 2 h and given to the patient to drink and bath [78]

Aqueous extract of the stem bark is taken orally [80]

Aqueous extract of the leaves taken orally [82]

Leaves It is used in combination with another recipe of plant origin [84]

Leaves Extract from the leaves is taken orally [85]

Leaves Mixed with leaves of *Tagetes minuta* L. burned and the smoke is inhaled [88]

Liliaceae *Allium cepa Linn* Bulb Paste [91]. Onion paste

Stem bark

Stem bark

Leaves and stem

**Scientific validation**

The extract reduced the locomotive activity, rearing and sniffing in rats [78]

The extract reduced the psychotic behavior characterized by anorexia and agitation in rats

[81]

It has sedative effect [83]

The extract inhibited stereotype behavior and spontaneous motor activity [84]

Attenuation of locomotory activity and dopamine levels

Leaf extracts exhibited SSRI activity and MAO-B inhibitory activity [63, 89]

inhibited dopaminergic neurotransmission and possibly blocks dopamine D2 receptor [91]

[85]

**Toxicity Phytonutrients**

The Ambit of Phytotherapy in Psychotic Care http://dx.doi.org/10.5772/intechopen.79547

No record

Linalool [83]

Alkaloids,

tannins [84]

Eugenol, cardinene, cubenol, borneol, linolenic acid, oleic acid, palmitric acid, steric acid, vallinin, vicenin, vitexin, vllinin acid, orientin, circineol, gallic acid, vitamin A, vitamin C, phosphorus and iron [87]

Flavones and flavanone derivatives [90]

Phenolic acid, flavonoids, anthocyanin, sterols, vitamins, pectin and peptides [91].

anthraquinones, cardiac glycosides, cyanogenetic glycosides, flavonoids, saponins, steroids and

Alkaloids, tannins, saponins, flavonoids, triterpenoid, phytosterols and glycosides [79]

77

Non -toxic [79]

Mildly toxic and has reducing effects on weight [80]

No records

No records

Nontoxic [86]

No record

Nontoxic [92]


**Family Species Parts Folkloric** 

*campanulatu*s F.M. Leighton

76 Psychosis - Biopsychosocial and Relational Perspectives

Alliaceae *Agapanthus* 

Amaryllidaceae *Boophane disticha*

Anacardiaceae *Spondias mombin* L.

Apocynaceae *Rauvolfia* 

Apocynaceae *Rauvolfia*

Asclepiadaceae *Gomphocarpus* 

Asclepiadaceae *Xysmalobium* 

Euphorbiaceae *Securinega virosa*

Baill.

*vomitoria* Afzel.

*tetraphylla* L.

*physocarpus* E. Mey

*undulatum* (L.) Aiton.f.

(Roxb ex. Willd)

(L.f.) herb

**usage**

of the root is taken orally [62]

Decoctions of bulb scales given to sedate violent, psychotic patents [65]

Root Decoction

Leaves and bulbs

Leaves Leaves extract is used traditionally [67]

Root The root is ground into powder and taken with pap or decoctions orally taken [68]

Leaves Powdered leaf is used to sedate psychotic patient [65]

Root Roots

Leaves and root

administered [74]

Decoction of the leaves and roots [76]

**Scientific validation**

Affinity to the serotonin transporter protein [66]; It also inhibited serotonin, noradrenalin and dopamine transporters [64]

The aqueous extract prolonged the sleeping time and decreased the stereotyped behavior [67]

Decreased locomotor behavior [69]

for 5-HT2A and DA-D2 receptors

The extract inhibited monoamine oxidase [72]

The extract exhibited significant effect on D1 receptor by inhibiting grooming and climbing behaviors in rats [76].

Extracts exhibited SSRI activity [64]

Leaves No record Significant affinity

[71]

Extract exhibited serotonin, noradrenalin, and dopamine transporter inhibitors [63, 64].

**Toxicity Phytonutrients**

Flavonoid [64]

Alkaloids (buphanidrine and buphanamine) [64]

Tannins, anthraquinones, flavonoids, glycosides. Phenols, saponins, phlobatannins and alkaloids [67]

Beta-carboline alkaloid,

11demethoxyreserpiline

10-demethoxyreserpiline (4), α-yohimbine (5) and reserpiline [71]

Carbohydrates, cardiac glycosides, steroids/ terpenoids, alkaloids and

Flavonoid (xysmalorin and uzarin) [64]

Alkaloids, saponin, flavonoid, and tannin [76]

alstonine [69]

(3) and

phenols [73]

No record

No record

Nontoxic [67]

Nontoxic [70]

Nontoxic [71]

No record

No toxicity [75]

Nontoxic [77]


**Active compound Mechanism of action References** Isoquinoline (alkaloid) Opioid receptor binding [107] Pyridine (alkaloid) Agonist nicotinic acetylcholinesterase receptor binding [108]

acetylcholinesterase receptor binding

Affinity to the serotonin transporter (SERT) protein [66]

Affinity for GABAA-benzodiazepine receptor [110]

Pilocarpine (alkaloid) Muscarinic acetylcholinesterase receptor agonist [105] Reserpine (alkaloid) Irreversible blockage of norepinephrine and dopamine [110] β-Sesquiphellandrene (terpene) Inhibition of dopamine neurotransmission at D1/D2 receptors [93]

Xysmalorin and uzarin (flavanoids) Affinity for SERT in the binding assay. [64]

Atropine (alkaloid) CNS depressants and competitively antagonize muscarinic cholinergic receptors.

Scopolamine (alkaloid) CNS depressants and competitively antagonize muscarinic cholinergic receptors.

**Figure 1.** A unified mechanism of actions of antipsychotic phytonutrients. MP, medicinal plants.

[109]

79

The Ambit of Phytotherapy in Psychotic Care http://dx.doi.org/10.5772/intechopen.79547

[111]

[111]

Physostigmine (alkaloid) Cholinesterase inhibitor and direct agonistic nicotinic

Buphanidrine and buphanamine

Agathisflavone and amentoflavone

**Table 3.** Psychoprotective bioactive metabolites.

(alkaloids)

(flavanoid)

**Table 2.** Medicinal plants list of plant with antipsychotic potential, their ethnopharmacology, toxicity and mechanism of actions.



**Table 3.** Psychoprotective bioactive metabolites.

**Family Species Parts Folkloric** 

78 Psychosis - Biopsychosocial and Relational Perspectives

Banks ex. Gaertn.f.

Ochnaceae *Lophira alata*

Piperaceae *Piper guineense*

Rutaceae *Ruta graveolens* L.

Solanaceae *Datura* 

of actions.

Schum & Thonn

*stramonium L.*

Geranial, neral and 6-methyl-5-hepten-2-one, citronellal, geranyl-acetate, β-caryophyllene and β-caryophylleneoxide, and 1,8 cineole (terpene)

**usage**

Fresh stembark is powdered with *Afzelia africana* stembark. It is then infused in water for 2 h and given to the patient to drink and bath [78].

Fruit No record Significant

of the leaves and oil extract are used [95]

Information not provided [65, 97]

Leaves Decoction

Leaves and seeds

Ursolic acid (terpene) Activation of dopamine D1

Stem bark

**Scientific validation**

The extract reduced locomotive activity and rearing in rats [78]

reduction on rearing, locomotor activity and dips in mice [93]

It exhibited MAO inhibitory activity

The seeds and leaves of *D. stramonium* are used to sedate psychotic patients [98]

and D2

Nicotinic and muscarinic cholinergic receptor binding properties in human brain tissue, acetylcholinesterase inhibitory properties and inhibition of enzyme GABA transaminase,

[89]

**Table 2.** Medicinal plants list of plant with antipsychotic potential, their ethnopharmacology, toxicity and mechanism

**Active compound Mechanism of action References**

Reserpiline(alkaloid) inhibition binding to DA-D2 and 5-HT2A receptors [71] α-Yohimbine (alkaloid) inhibition binding to DA-D2 and 5-HT2A receptors [71]

Polygalasaponins (saponin) Affinity for dopamine and serotonin receptors [101]

leading to increased GABA activity

Tropane (alkaloid) Muscarinic acetylcholinesterase receptor antagonist [105]

Methylaplysinopsin (alkaloid) Inhibition of monoamine oxidase (MAO) and displacement serotonin from its receptors

Yuanzhi-1 (triterpenoid saponin) Uptake of inhibitor that block dopamine, norepinephrine and serotonin transporters

Purine (alkaloid) Receptor interactions, specifically involving DA D1 receptor signaling

**Toxicity Phytonutrients**

Alkaloids, tannins, saponins, flavonoids, triterpenoid, phytosterols and glycosides [79]

β-Sesquiphellandrene, limonene, linalool [93]

Furocoumarins, furoquinolines and acridone alkaloids [89].

Alkaloids, tannins, saponins and cardiac glycosides [97]

[100]

[102]

[106]

[103, 104]

Nontoxic [79]

Nontoxic [94]

No toxicity [96]

Toxic [97]

receptors [99]

**Figure 1.** A unified mechanism of actions of antipsychotic phytonutrients. MP, medicinal plants.

Taken together, a unified mechanism of actions of the antipsychotic phytonutrients could be proposed as presented in **Figure 1**. This may be conceptualized to potentiate either (a) modulatory role on dopamine D1 and D2 receptors, (b) regulation of serotonin reuptake/transporters, (c) inhibitory effect on the specific activity of monoamine oxidase, or (d) regulation of the specific activities of acetylcholinesterase and Gama-aminobutyric acid transaminase. Plants endowed with these metabolites (**Figure 1**) may unilaterally or synergistically be employed with other conventional antipsychotic therapies to achieve optimal results in alleviating the ill episodes of the different forms (depression, hallucination, schizophrenia, etc.) of psychosis related disorders.

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